Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/111430
Title: XIAP inhibitors induce differentiation and impair clonogenic capacity of acute myeloid leukemia stem cells.
Author: Moreno-Martínez, Daniel
Nomdedeu i Fàbrega, Meritxell
Lara Castillo, María Carmen
Etxabe, Amaia
Pratcorona, Marta
Tesi, Niccolò
Díaz-Beyá, Marina
Rozman, María
Montserrat Costa, Emilio
Urbano Ispizua, Álvaro
Esteve, Jordi
Risueño, Ruth M.
Keywords: Leucèmia mieloide
Medicaments
Cèl·lules mare
Farmacologia
Hematologia
Myeloid leukemia
Drugs
Stem cells
Pharmacology
Hematology
Issue Date: 30-Jun-2014
Publisher: Impact Journals
Abstract: Acute myeloid leukemia (AML) is a neoplasia characterized by the rapid expansion of immature myeloid blasts in the bone marrow, and marked by poor prognosis and frequent relapse. As such, new therapeutic approaches are required for remission induction and prevention of relapse. Due to the higher chemotherapy sensitivity and limited life span of more differentiated AML blasts, differentiation-based therapies are a promising therapeutic approach. Based on public available gene expression profiles, a myeloid-specific differentiation-associated gene expression pattern was defined as the therapeutic target. A XIAP inhibitor (Dequalinium chloride, DQA) was identified in an in silico screening searching for small molecules that induce similar gene expression regulation. Treatment with DQA, similarly to Embelin (another XIAP inhibitor), induced cytotoxicity and differentiation in AML. XIAP inhibition differentially impaired cell viability of the most primitive AML blasts and reduced clonogenic capacity of AML cells, sparing healthy mature blood and hematopoietic stem cells. Taken together, these results suggest that XIAP constitutes a potential target for AML treatment and support the evaluation of XIAP inhibitors in clinical trials.
Note: Reproducció del document publicat a: https://doi.org/10.18632/oncotarget.2016
It is part of: Oncotarget, 2014, vol. 5, num. 12, p. 4337-4346
Related resource: https://doi.org/10.18632/oncotarget.2016
URI: http://hdl.handle.net/2445/111430
ISSN: 1949-2553
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Medicina)

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